The objectives of this proposal are to design, synthesize, and evaluate the biochemistry and pharmacology of a series of potential mechanism-based irreversible inhibitors of diamine oxidase (histaminase). The inhibitors to be prepared, beta-gamma-unsaturated amine and beta-fluoroamine analogs and homologs of histamine, will be investigated in vitro for both specificity and mechanism of inhibition. Active compounds will be evaluated in tissue-distribution studies by both in vivo uptake and enzyme inhibition with respect to time and dosage. From these studies, new information can be ascertained. This knowledge may be of clinical value especially for medullary carcinoma of the thyroid and small cell carcinoma of the lung where the activity of this enzyme is significantly elevated.